Planta Med 2014; 80 - P1L31
DOI: 10.1055/s-0034-1394689

Antimycobacterial potential of benzophenanthridine-based derivatives

X Luo 1, JA Aínsa 2, B Gracia 2, A Paterna 1, M Reis 1, S Mulhovo 3, MJU Ferreira 1
  • 1Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. D. Forças Armadas, 1600 – 083, Lisboa, Portugal
  • 2Department of Microbiology, Faculty of Medicine, University of Zaragoza, C/Domingo Miral s/n, 50009 Zaragoza, Spain
  • 3Centro de Estudos Moçambicanos e de Etnociências, Universidade Pedagógica, 21402161 Maputo, Mozambique

Semi-synthesis of natural products has been considered to be an optional method for providing more active and less toxic derivatives and establishment of structure-activity relationships (SAR). The genus Zanthoxylum is a rich source of benzophenanthridine-type alkaloids. In our search for antimycobacterial constituents from medicinal plants, we have extensively investigated the medicinal African plant Zanthoxylum capense, which has led to the isolation of twenty-seven compounds most of them benzophenanthridine-type alkaloids. Benzophenanthridine alkaloids were found to have various biological activities such as anti-leukemic, anti-microbial, anti-inflammatory, and anti-hypertensive activities [1]. During our study, some of the isolated benzophenanthridine alkaloids showed promising antimycobacterial activity as well as antibacterial activity [2,3]. Decarine was isolated in a large amount from the methanolic extract of Z. capense, which allowed its use as a natural product scaffold in the generation of a small benzophenanthridine-based compounds library. The esterification of decarine with different acylating agents produced seventeen alkanoyl/aroyl esters in good yields. All the esters were evaluated for their antimycobacterial activity against Mycobacterium tuberculosis H37Rv at a concentration range of 0.024 – 50 µg/mL. Four derivatives exhibited comparable antimycobacterial activity to decarine (MIC 0.78 µg/mL), showing MIC values of 1.56 µg/mL. When analysing the structural features and the activity of these ester derivatives, we may deduce that esters with short alkanoyl side chain display better antimycobacterial activity than the ones with long ester side chains and with aroyl side chains.

Acknowledgements: This study was supported by FCT, Portugal (SFRH/BPD/37179/2007).

References:

[1] Adesina S.K. (2005) Afr J Tradit Complement Altern Med 2: 282 – 301.

[2] Luo X.; Pires D. et al. (2013)J. Ethnopharmacol. 146: 417 – 422.

[3] Luo X.; Pedro L. et al. (2012) Planta Med. 78: 148 – 153